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  • Breakthrough infections with the SARS-CoV-2 omicron (B.1.1.529) variant in patients with immune-mediated inflammatory diseases

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Epidemiology
Breakthrough infections with the SARS-CoV-2 omicron (B.1.1.529) variant in patients with immune-mediated inflammatory diseases
  1. Eileen W Stalman1,
  2. Luuk Wieske1,2,
  3. Koos P J van Dam1,
  4. Laura Y Kummer1,3,
  5. Zoé L E van Kempen4,
  6. Joep Killestein4,
  7. Adriaan G Volkers5,
  8. Sander W Tas6,
  9. Laura Boekel7,
  10. Gertjan J Wolbink8,9,
  11. Anneke J Van der Kooi1,
  12. Joost Raaphorst10,
  13. Mark Löwenberg5,
  14. R Bart Takkenberg5,
  15. Geert R A M D’Haens5,
  16. Phyllis I Spuls11,
  17. Marcel W Bekkenk12,
  18. Annelie H Musters12,
  19. Nicoline F Post12,
  20. Angela L Bosma12,
  21. Marc L Hilhorst13,
  22. Yosta Vegting13,
  23. Frederique J Bemelman13,
  24. Alexandre E Voskuyl14,
  25. Bo Broens15,
  26. Agner Parra Sanchez5,15,
  27. Cécile A C M van Els16,17,
  28. Jelle De Wit18,19,
  29. Abraham Rutgers20,
  30. Karina de Leeuw21,
  31. Barbara Horváth22,
  32. Jan J G M Verschuuren23,
  33. Annabel M Ruiter23,
  34. Lotte van Ouwerkerk24,
  35. Diane van der Woude25,
  36. C F Allaart26,
  37. Onno Y K Teng27,
  38. Pieter van Paassen28,
  39. Matthias H Busch29,
  40. Papay B P Jallah29,
  41. Esther Brusse30,
  42. Pieter A van Doorn30,
  43. Adája Elisabeth Baars30,
  44. Dirk Jan Hijnen31,
  45. Corine R G Schreurs31,
  46. W Ludo Van der Pol32,
  47. H Stephan Goedee32,
  48. Maurice Steenhuis3,
  49. Sofie Keijzer3,
  50. Jim B D Keijser3,
  51. Arend Boogaard3,
  52. Olvi Cristianawati3,
  53. Anja ten Brinke3,
  54. Niels J M Verstegen3,
  55. Koos A H Zwinderman33,
  56. Theo Rispens8,
  57. S Marieke van Ham8,
  58. Taco W Kuijpers34,
  59. Filip Eftimov35
  60. On behalf of the T2B! immunity against SARS-CoV-2 study group
  1. 1 Department of Neurology and Neurophysiology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  2. 2 Department of Clinical Neurophysiology, Sint Antonius Hospital, Nieuwegein, The Netherlands
  3. 3 Department of immunopathology, Sanquin Research, Amsterdam, The Netherlands
  4. 4 Department of Neurology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  5. 5 Department of Gastroenterology and Hepatology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  6. 6 Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  7. 7 Research, Reade, Amsterdam, The Netherlands
  8. 8 Immunopathology, Sanquin Research an Landsteiner Laboratory, Amsterdam, The Netherlands
  9. 9 rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands
  10. 10 Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  11. 11 Department of Dermatology, Public Health and Epidemiology, Immunity and Infections, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  12. 12 Department of Dermatology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  13. 13 Department of Internal Medicine, Section of Nephrology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  14. 14 Department of Rheumatology, Amsterdam UMC, Amsterdam, The Netherlands
  15. 15 Department of Rheumatology and Clinical Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  16. 16 Centre for Infectious Disease Control, National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands
  17. 17 Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  18. 18 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
  19. 19 Center for Infectious Diseases, National Institute for Public Health and the Environment, Utrecht, The Netherlands
  20. 20 Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands
  21. 21 Department of Rheumatology and Clinical Immunology, University Medical Center, University of Groningen, Groningen, The Netherlands
  22. 22 Dermatology, University Medical Center Groningen, Groningen, The Netherlands
  23. 23 Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  24. 24 Rheumatology, Leiden Universitair Medisch Centrum, Leiden, The Netherlands
  25. 25 Rheumatology, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  26. 26 Rheumatology, LUMC, Leiden, The Netherlands
  27. 27 Nephrology, Leiden University Medical Centre, Leiden, The Netherlands
  28. 28 Department of Internal Medicine/Devision of Clinical & Experimental Immunology, Maastricht University Medical Centre, Maastricht, The Netherlands
  29. 29 Department of Nephrology and Clinical Immunology, Maastricht Universitair Medisch Centrum+, Maastricht, The Netherlands
  30. 30 Department of Neurology, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands
  31. 31 Department of Dermatology, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands
  32. 32 Department of Neurology and Neurosurgery, University Medical Centre, Utrecht, The Netherlands
  33. 33 Clinical Research Unit, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  34. 34 Department of Pediatric Immunology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  35. 35 Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Dr Filip Eftimov, Department of Neurology, University of Amsterdam, Amsterdam 1105, Netherlands; f.eftimov{at}amsterdamumc.nl

Abstract

Objectives To compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.

Methods Data were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included. The observation period was between 1 January 2022 and 1 April 2022, during which the SARS-CoV-2 omicron (BA.1 and BA.2 subvariant) was dominant. A SARS-CoV-2 breakthrough infection was defined as a reported positive PCR and/or antigen test at least 14 days after primary immunisation. A multivariate logistic regression model was used to investigate determinants.

Results 1593 patients with IMID on immunosuppressants and 579 controls were included. The cumulative incidence of breakthrough infections was 472/1593 (29.6%; 95% CI 27% to 32%) in patients with IMID on immunosuppressants and 181/579 (31.3%; 95% CI 28% to 35%) in controls (p=0.42). Three (0.5%) participants had severe disease. Seroconversion after primary immunisation (relative risk, RR 0.71; 95% CI 0.52 to 0.96), additional vaccinations (RR 0.61; 95% CI 0.49 to 0.76) and a prior SARS-CoV-2 infection (RR 0.60; 95% CI 0.48 to 0.75) were associated with decreased risk of breakthrough infection.

Conclusions The cumulative incidence of reported SARS-CoV-2 omicron breakthrough infections was high, but similar between patients with IMID on immunosuppressants and controls, and disease severity was mostly mild. Additional vaccinations and prior SARS-CoV-2 infections may reduce the incidence of breakthrough infections.

  • Autoimmune Diseases
  • Covid-19
  • Autoimmunity
  • Vaccination

Data availability statement

Data are available on reasonable request. Aggregated data and code for reproducing the results of this analysis can be shared on reasonable request.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/ard-2022-222904

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    Data availability statement

    Data are available on reasonable request. Aggregated data and code for reproducing the results of this analysis can be shared on reasonable request.

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    Footnotes

    • Handling editor Josef S Smolen

    • EWS and LW contributed equally.

    • Contributors All authors met the criteria for authorship set by the International Committee of Medical Journal Editors. TR, MS, SK, JK, AB and OC did the serological assays; all other authors contributed in data acquisition. EWS, LW, TWK and FE wrote the first draft of the manuscript. EWS and LW did the data analyses. EWS, LW, PJKvD and LYK had full access to and verified the underlying data. All authors helped to revise the manuscript for important intellectual content and had final responsibility for the decision to submit for publication. TWK and FE are joint last authors. FE was the guarantor.

    • Funding This study was supported by ZonMw (The Netherlands Organization for Health Research and Development, grant 10430072010007). The sponsor had no role in the design, analyses or reporting of the study.

    • Competing interests FE and TWK report (governmental) grants from ZonMw to studyimmune response after SARS-Cov-2 vaccination in autoimmune diseases.FE also reports grants from Prinses Beatrix Spierfonds, CSL Behring,Kedrion, Terumo BCT, Grifols, Takeda Pharmaceutical Company, andGBS-CIDP Foundation; consulting fees from UCB Pharma and CSlBehring; and honoraria from Grifols. AJvdK reports grants from CSLBehring and participation on an advisory board for Argen-X. ML reports agrant from Galapagos not related to this study, and honoraria from BristolMyers Squibb, Pfizer, Takeda, and Tillotts. PIS is involved in clinical trialswith many pharmaceutical industries that manufacture drugs used for thetreatment of, for example, psoriasis and atopic dermatitis, for whichfinancial compensation is paid to the department or hospital, and is achief investigator of the TREAT NL registry taskforce and SECURE-ADregistry. MWB is a secretary for the Dutch Experimental DermatologyBoard; head of the pigmentary disorders group within the DutchDermatology Board; and reports honoraria from Pfizer, Sanofi, Novartis,and Fondation René Touraine. JK has speaking relationships with MerckSerono, Biogen Idec, TEVA, Sanofi, Genzyme, Roche, and Novartis;received financial support to his institution for researchactivities from Merck Serono, Bayer Shcering Pharma, Biogen Idec,GlaxoSmithKline (GSK), Roche, Teva, Sanofi, Genzyme, and Novartis. BHreports unpaid positions as a medical adviser for several patient groups, aboard position for ERN-SKIN, and associate editor for The British Journalof Dermatology; reports grants from AbbVIe, Akari Therapeutics, Celgene, and Novartis; consulting fees from UCB Pharma, Novartis, and Janssen; and honoraria from AbbVie. JJGMV reports consulting fees from Argenx,Alexion, and NMD Pharma, and is a co-inventor on patent applicationsbased on MuSK-related research. DJH reportsgrants from AbbVie, AstraZeneca, Janssen, LEO Pharma, and UCB;honoraria from AbbVie, Galderma, Janssen, Lilly, Pfizer, Sanofi, and UCB;and a paid position on an advisory board for BIOMAP IMI. PAvDparticipated on an advisory board for Octapharma. PvP reports grantsfrom Alexion Pharma and GSK, and participation on advisory boards forGSK and Vifor Pharma. GRAMD’H reports consulting fees from AbbVie,Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, BristolMyers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, ExeliomBiosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido,Roche, Gilead, GSK, Gossamerbio, Pfizer, Immunic, Johnson andJohnson, Origo, Polpharma, Procise Diagnostics, PrometheusLaboratories, Prometheus Biosciences, Progenity, and Protagonist;honoraria from AbbVie, Arena, Galapagos, Gilead, Pfizer, Bristol MyersSquibb, and Takeda; and participation on advisory boards for AbbVie,Seres Health, Galapagos, and AstraZeneca. RBT reports honoraria fromSobi and Norgine, and participation on an advisory board for Norgine.SHG is a board member of the Dutch Society of Clinical Neurophysiology(unpaid), reports grants from Prinses Beatrix Spierfonds, and receivedspeaker fees from Shire/Takeda. KAHZ reports paid data safetymonitoring board positions for Torrent and Foresee. All other authorsdeclare no competing interests.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.